Mast cells/basophils in the peripheral blood of allergic individuals who are HIV-1 susceptible due to their surface expression of CD4 and the chemokine receptors CCR3, CCR5, and CXCR4

Abstract

IntroductionMast cells (MCs) and basophils are histamine-containing, metachromatic granulocytes that express the high-affinity IgE receptor, Fc⑀RI, on their surfaces. 1,2 When activated via this receptor, both populations of cells immediately exocytose their granule constituents and then more slowly generate and release cytokines, chemokines, and arachidonic acid metabolites. Thus, these granulocytes play extremely important roles in IgE-mediated inflammatory responses. Although human MCs and basophils are similar in certain aspects, their substantial biochemical and morphologic differences in normal individuals have led to the concept that the 2 populations of cells probably are developmentally unrelated. MCs, for example, reside in tissues and generally possess a centrally positioned, oval nucleus. In contrast, basophils generally reside in the blood and contain a segmented nucleus. The MCs in the lung and skin of most normal individuals contain chymase, carboxypeptidase A, elastase, cathepsin G, and multiple tryptases in their granules. [3][4][5][6][7][8][9][10][11][12][13] Basophils in the peripheral blood of most normal individuals contain cathepsin G and elastase 4 but lack carboxypeptidase A and chymase. 14,15 Tryptase has been detected in normal human basophils. However, in the initial reports, Schwartz and coworkers concluded that normal human MCs contain on average about 250-fold more tryptase protein 16 and about 50 000-fold more tryptase messenger RNA (mRNA) 15 than normal human basophils.Although it was originally thought that the phenotype of a MC was fixed and irreversibly predetermined before its progenitor exited the bone marrow, it is now apparent that human and mouse 26 The developmental relationship between basophils and MCs remains unclear, in part, because no defined biochemical marker has been identified that can distinguish these 2 populations of cells in an animal that can be experimentally manipulated. A population of Fc⑀RI ϩ /metachromatic cells that possesses segmented nuclei is present in the peripheral blood of helminth-infected mice. Because of their location and nuclear profiles, it was originally thought that these mouse cells were basophils; however, recent studies have shown that they are actually senescent MCs trafficking from the jejunum to the spleen. 27 We have described a population of cells with both MC and basophil features in the blood of patients with asthma, allergy, and allergic drug reactions. 28 For personal use only. on May 10, 2018. by guest www.bloodjournal.org From cells resemble normal mature basophils in terms of their peripheral blood location, segmented nuclei, and surface expression of the Bsp-1 epitope. However, they more closely resemble normal mature MCs in terms of their surface expression of CD117 (c-kit) and their granule expression of multiple proteases.In the current study, we present additional biochemical evidence that the unusual population of metachromatic cells we identified in the blood of patients with various allergic disorders belongs in...

The CD4 molecule on CD8+T lymphocytes directly enhances the immune response to viral and cellular antigens

“…Together, these events could provide a mechanism through which CD4 directly modulates CD8 ϩ CTL function. Interestingly, the CD4 molecule has been found, under various conditions, on a subset of hematopoietic progenitor cells (28,29), B cells (30), NK cells (31), eosinophils (32), monocytes (33), neutrophils (34), mast cells͞basophils (35), and microglia (36). Our current studies specifically examine the function of CD4 only on purified CD8 ϩ T cells, and further studies are required to fully define the complex role that this molecule plays in the immune response.…”

HIV-1 Envelope gp41 Peptides Promote Migration of Human FcεRI+ Cells and Inhibit IL-13 Synthesis Through Interaction with Formyl Peptide Receptors

“…ϩ cells could be involved in HIV-1 infection in a variety of ways (11)(12)(13)(14)(15)(16). In fact, we have demonstrated that gp120 from divergent HIV-1 isolates from different clades interacts with the V H 3 region of IgE on human Fc⑀RI ϩ (9, 47).…”

“…Moreover, Tat protein up-regulates the level of CCR3 mRNA and surface expression of CCR3 on human basophils (10). Recent evidence suggests that a population of basophils and/or mast cells in peripheral blood can be infected in vitro by M-tropic strains of HIV-1 (11,12). Consequently, human Fc⑀RI ϩ cells are important in HIV-1 infection (13)(14)(15)(16).…”

“…No natural FPRL2 agonists have been identified. However, it has been demonstrated that Helicobacter pylori peptide Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) activates the monocyte via FPRL2 (34).…”

RasGRP4, a New Mast Cell-restricted Ras Guanine Nucleotide-releasing Protein with Calcium- and Diacylglycerol-binding Motifs

“…Although these and other findings document that MCs play beneficial immunosurveillance and effector roles in the body, it has been known for some time that MCs also exhibit adverse roles in numerous inflammatory disorders including asthma, chronic urticaria, and systemic anaphylaxis. Recent studies (7)(8)(9) have revealed that these effector cells also participate in the pathogenesis of AIDS.…”